Sex-specific DNA-replication in the early mammalian embryo.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
27 Jul 2024
Historique:
received: 31 08 2023
accepted: 18 07 2024
medline: 27 7 2024
pubmed: 27 7 2024
entrez: 26 7 2024
Statut: epublish

Résumé

The timing of DNA replication in mammals is crucial for minimizing errors and influenced by genome usage and chromatin states. Replication timing in the newly formed mammalian embryo remains poorly understood. Here, we have investigated replication timing in mouse zygotes and 2-cell embryos, revealing that zygotes lack a conventional replication timing program, which then emerges in 2-cell embryos. This program differs from embryonic stem cells and generally correlates with transcription and genome compartmentalization of both parental genomes. However, consistent and systematic differences existed between the replication timing of the two parental genomes, including considerably later replication of maternal pericentromeric regions compared to paternal counterparts. Moreover, maternal chromatin modified by Polycomb Repressive Complexes in the oocyte, undergoes early replication, despite belonging to the typically late-replicating B-compartment of the genome. This atypical and asynchronous replication of the two parental genomes may advance our understanding of replication stress in early human embryos and trigger strategies to reduce errors and aneuploidies.

Identifiants

pubmed: 39060312
doi: 10.1038/s41467-024-50727-w
pii: 10.1038/s41467-024-50727-w
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

6323

Subventions

Organisme : Danmarks Grundforskningsfond (Danish National Research Foundation)
ID : DNRF115
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : NNF22OC0080710

Informations de copyright

© 2024. The Author(s).

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Auteurs

Jason Alexander Halliwell (JA)

DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. jhalliwell@sund.ku.dk.

Javier Martin-Gonzalez (J)

Core Facility for Transgenic Mice, Department of Experimental Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Adnan Hashim (A)

Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Centre for Embryology and Healthy Development, University of Oslo, Oslo, Norway.

John Arne Dahl (JA)

Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Centre for Embryology and Healthy Development, University of Oslo, Oslo, Norway.

Eva R Hoffmann (ER)

DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. eva@sund.ku.dk.

Mads Lerdrup (M)

DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. mlerdrup@sund.ku.dk.
Centre for Embryology and Healthy Development, University of Oslo, Oslo, Norway. mlerdrup@sund.ku.dk.

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